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Central Fatigue Induced by Losartan Involves Brain Serotonin and Dopamine Content


Medicine & Science in Sports & Exercise: August 2010 - Volume 42 - Issue 8 - p 1469-1476
doi: 10.1249/MSS.0b013e3181d03d36
Basic Sciences

Purpose: To investigate the influence of angiotensin II (Ang II) AT1 receptors blockade on central fatigue induced by brain content of serotonin (5-HT) and dopamine (DA) during exercise.

Methods: Losartan (Los) was intracerebroventricularly injected in rats before running until fatigue (n = 6 per group). At fatigue, brains were quickly removed for measurement of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), DA, and 3,4-dihydroxyphenylacetic acid by high-pressure liquid chromatography in the preoptic area, hypothalamus, hippocampus, and frontal cortex.

Results: Intracerebroventricular injection of Los increased 5-HT content in the preoptic area and hypothalamus. Such results correlated positively with body heating rate and inversely with time to fatigue. On the other hand, time to fatigue was directly correlated with the diminished concentration of 5-HT in the hippocampus of Los rats. Although the levels of DA were not affected by Los treatment during exercise in any of the brain areas studied, a higher 5-HT/DA ratio was seen in the hypothalamus of Los animals. This higher hypothalamic 5-HT/DA ratio correlated positively with body heating rate and negatively with time to fatigue.

Conclusions: Our results show that central fatigue due to hyperthermia and increased body heating rate induced by central Ang II AT1 receptor blockade in exercising rats is related with higher 5-HT content in the preoptic area and hypothalamus as well as with decreased levels of this neurotransmitter in the hippocampus. Furthermore, the interaction between 5-HT and DA within the hypothalamus seems to contribute to hyperthermia and premature central fatigue after angiotensinergic inhibition.

1Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Minas Gerais, BRAZIL; 2Institute of Biological and Health Sciences, Pontifícia Universidade Católica, Minas Gerais, BRAZIL; and 3Department of Physical Education, School of Physical Education, Physical Therapy and Occupational Therapy, Federal University of Minas Gerais, Minas Gerais, BRAZIL

Address for correspondence: Cândido C. Coimbra, Ph.D., Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas/UFMG, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil; E-mail:

Submitted for publication September 2009.

Accepted for publication December 2009.

©2010The American College of Sports Medicine